LHRH is a very potent mammalian neurohormone. It is released from the hypothalamus resulting in the highly defined surge of LH involved with ovulation. Recent reports have evidenced hypothalamic, pituitary and serum enzymatic activity capable of rapidly inactivating LHRH. The present studies are designed to investigate the possibility that fluctuations in LHRH degrading activity may play a role in establishing hypothalamic LHRH levels and therefore the amount of LHRH which may be potentially released to act on the pituitary. The investigations would establish the course of hypothalamic enzyme activity over the course of the estrus cycle and determine if decreased degratory activity is associated with increased hypothalamic LHRH prior to the proestrus LH surge and if increased activity is associated with decreased LHRH subsequent to the LH surge. The proposed studies will also determine if steroid and LH injections are capable of modulating hypothalamic LHRH degradation. Hypothalamic perifusion experiments will determine if fluctuations in LHRH release occur over the course of estrus cycle. Fractionation experiments will determine if more than one peak of degratory activity is separable from a given source and if the activities from dfferent sources are similar physically and kinetically. The LHRH degratory capacity of dispersed pituitary cell cultures will also be investigated. An understanding of the factors capable of modulating LHRH secretion and therefore gonadotropin secretion is imperative in understanding the reproductive cycle and in attempts to develop new therapeutic procedures of contraception.